Two closely related enzymes may be targets for the treatment of lung cancer, according to a study at the University of Gothenburg, Sweden, by a research team at Sahlgrenska Academy.

Published in the journal Proceedings of the National Academy of Sciences, the discovery entailed blocking production of the two enzymes in transgenic mice. The result was slower cell growth, fewer tumors and improved survival rates for the rodents without causing side effects in the healthy lung cells.

Researchers explained that many cancers entail RAS and RHO proteins which contribute to the growth and spread of tumors. These are stimulated by FTase and GGTase-I, which are related enzymes. Previous attempts by drug firms to block these enzymes have had mixed results.

"We therefore developed genetic strategies in mice, known as transgenic mice, to switch off the genes coding for FT and GGT, enabling us to investigate whether a complete blockade of FT or GGT can inhibit the development of lung cancer, and whether this has side effects in the lungs," explains researcher Anna-Karin Sjögren, who led the study together with Meng Liu, both from the Department of Clinical and Molecular Medicine.

In experiments where both genes were switched off at the same time, the number of lung tumors dropped sharply and the mice lived much longer. This means that the absence of these two enzymes does not have any obvious side effects in the lungs, and that lung tumor cells seem to be more sensitive to the treatment than normal lung cells.

"Our findings show that these are promising targets for the treatment of lung cancer," conclude the researchers.
Sources: Proceedings of the National Academy of Sciences ( www.pnas.org ) / www.gu.se